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有机化学
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有机化学 ›› 2011, Vol. 31 ›› Issue (12): 2135-2139. 上一篇    下一篇

研究简报

单螺环哌嗪季铵盐类化合物的合成及镇痛活性研究

刘文俊，王欣*，李刚，叶加，程铁明，李润涛*   

  1. (北京大学药学院天然药物及仿生药物国家重点实验室 北京 100191)
  • 收稿日期:2011-03-23 修回日期:2011-06-14 发布日期:2011-07-27
  • 通讯作者: 王欣 E-mail:xinwang@bjmu.edu.cn

Synthesis and Analgesic Activity of Mono-spirocyclopiperazinium Analogues

LIU Wen-Jun, WANG Xin, LI Gang, YE Jia, CHENG Tie-Ming, LI Run-Tao   

  1. (State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking Uni-versity, Beijing 100191)
  • Received:2011-03-23 Revised:2011-06-14 Published:2011-07-27
  • Contact: vivian Wang E-mail:xinwang@bjmu.edu.cn

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被引次数

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为寻找镇痛活性更好的化合物, 以前期发现的螺环哌嗪季铵盐类化合物1为先导物, 设计合成了8个未见文献报道的衍生物. 通过1H NMR, 13C NMR和元素分析或高分辨质谱确定了化合物的结构. 利用小鼠醋酸扭体模型初步评价了它们的镇痛活性, 构效关系研究表明, 苯环上的羟基是关键的药效团, 与开链季铵盐相比, 螺环季铵盐结构对活性更有利|扩大螺环和引入取代基对活性不利.

关键词: 单螺环哌嗪季铵盐, 镇痛活性, 合成, Mannich反应, 构效关系

In order to find more potent analgesics, eight new mono-spirocyclopiperazinium analogues were designed and synthesized by selecting compound 1 as lead compound, which was obtained from our previous works. The structures of target compounds were characterized by 1H NMR, 13C NMR spectra and elemental analysis or HRMS. The synthesized compounds were evaluated for their in vivo analgesic activity by acetic acid induced writhing test. The results indicate that hydroxyl group on the aryl ring is the key pharmacophore and spirocycloammonium salt framework is favorable for the activity. Enlarging the spiro-ring or introducing substituted group is at a disadvantage.

Key words: mono-spirocyclopiperazinium, analgesic activity, synthesis, Mannich reaction, structure-activ- ity relationship